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Clinical Trial
. 2012 Apr;23(4):377-81.
doi: 10.1089/hum.2011.220. Epub 2012 Apr 10.

Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease

Gabriele Mittermeyer  1 , Chadwick W Christine, Kathryn H Rosenbluth, Suzanne L Baker, Philip Starr, Paul Larson, Paul L Kaplan, John Forsayeth, Michael J Aminoff, Krystof S Bankiewicz
Affiliations
Clinical Trial

Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease

Gabriele Mittermeyer et al. Hum Gene Ther. 2012 Apr.

Abstract

We report the results of a long-term follow-up of subjects in a phase 1 study of AAV2-hAADC (adeno-associated virus type 2-human aromatic L-amino acid decarboxylase) gene therapy for the treatment of Parkinson's disease (PD). Ten patients with moderately advanced PD received bilateral putaminal infusions of either a low or a high dose of AAV2-hAADC vector. An annual positron emission tomography (PET) imaging with [(18)F]fluoro-L-m-tyrosine tracer was used for evaluation of AADC expression, and a standard clinical rating scale [Unified Parkinson's Disease Rating Scale (UPDRS)] was used to assess effect. Our previous analysis of the 6-month data suggested that this treatment was acutely safe and well tolerated. We found that the elevated PET signal observed in the first 12 months persisted over 4 years in both dose groups. A significantly increased PET value compared with the presurgery baseline was maintained over the 4-year monitoring period. The UPDRS in all patients off medication for 12 hr improved in the first 12 months, but displayed a slow deterioration in subsequent years. This analysis demonstrates that apparent efficacy continues through later years with an acceptable safety profile. These data indicate stable transgene expression over 4 years after vector delivery and continued safety, but emphasize the need for a controlled efficacy trial and the use of a higher vector dose.

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Figures

FIG. 1.
FIG. 1.
Time course of FMT-PET. (A) Time course of PET signal in low-dose (blue) or high-dose (red) subjects over time. (B, C) Scans of high-dose patient at baseline (B) and 4 years after treatment (C). Color images available online at www.liebertonline.com/hum
FIG. 2.
FIG. 2.
Time course of UPDRS ON and OFF scores. (A, B) OFF (A) and ON (B) scores for individual study subjects over time for low dose (blue) and high dose (red). (C, D) Aggregate OFF (C) and ON (D) scores for low-dose (blue) and high-dose (red) subjects. Color images available online at www.liebertonline.com/hum
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Comment in

References

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